(S)-5-溴-3-((1-甲基吡咯烷-2-基)甲基)-1H-吲哚 | 208464-41-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: (S)-5-溴-3-((1-甲基吡咯烷-2-基)甲基)-1H-吲哚
• 英文名称: (S)-5-Bromo-3-[(N-methylpyrrolidin-2-yl)methyl]-1H-indole
• 英文别名: (S)-5-Bromo-3-((1-methylpyrrolidin-2-YL)methyl)-1H-indole；5-bromo-3-[[(2S)-1-methylpyrrolidin-2-yl]methyl]-1H-indole
• CAS: 208464-41-9
• 化学式: C₁₄H₁₇BrN₂
• 分子量: 293.206
• InChiKey: JCXOJXALBTZEFE-LBPRGKRZSA-N

物化性质

• 沸点：
  412.9±25.0 °C(Predicted)
• 密度：
  1.418±0.06 g/cm3(Predicted)
• 溶解度：
  二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-5-溴-3-((1-甲基吡咯烷-2-基)甲基)-1H-吲哚 在 四(三苯基膦)钯 sodium hydroxide 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 15.0h， 生成 (S)-5-(1-aza-1-tert-butoxycarbonylcyclohex-3-en-4-yl)-3-[(N-methylpyrrolidin-2-yl)methyl]-1H-indole
  参考文献：
  名称：

  5-CYCLO INDOLE COMPOUNDS AS 5-HT1D RECEPTOR LIGANDS

  摘要：

  公开号：

  EP0944595B1
• 作为产物：
  描述：

  (S)-2-(5-溴-1H-吲哚-3-羰基)吡咯烷-1-羧酸苄酯 以57%的产率得到(S)-5-溴-3-((1-甲基吡咯烷-2-基)甲基)-1H-吲哚
  参考文献：
  名称：

  5-cyclo indole compounds

  摘要：

  本文描述的是对5-HT.sub.1D-类受体具有选择性的化合物，其具有以下通式：##STR1##其中A选自一个六元非芳香族、可选择性取代的碳环和一个六元非芳香族、可选择性取代的杂环，其中含有一个或两个来自O、S、SO、SO.sub.2和N.sup.4的杂原子；R.sup.1选自H和OH；n根据化学结构允许为0或1；R.sup.2选自CR.sup.5 CR.sup.6 CH.sub.2 NR.sup.7 R.sup.8或具有以下式II、III或IV的基团：##STR2##R.sup.3选自H和苯甲酰基；R.sup.4选自H、较低烷基、苄基、较低烷基羰基、较低烷基氨基羰基、较低烷基氨基硫氨基羰基、较低烷酰基、较低烷基氨基亚胺和较低烷氧基取代的较低烷基烯；R.sup.5和R.sup.6独立选自H、较低烷氧基和羟基；R.sup.7和R.sup.8独立选自H和较低烷基，或者R.sup.7和R.sup.8形成一个与它们附着的氮原子一起构成一个可选择性取代的3-至6-成员环的烷基桥；表示单键或双键；R.sup.9、R.sup.10和R.sup.11独立选自H和较低烷基。还描述了将这些化合物用作药物来治疗刺激5-HT.sub.1D-类受体所涉及的症状，如偏头痛。

  公开号：

  US05998438A1

文献信息

• SYNTHESIS OF 3--5-[2-(PHENYLSULFONYL)ETHYL]-1H-INDOLE
  申请人：Serafini Siro

  公开号：US20110166364A1

  公开（公告）日：2011-07-07

  The present invention refers to the synthesis of 3-[(2R)-1-methylpyrrolidin-2-yl]methyl}-5-[2-(phenylsulfonyl)ethyl]-1H-indole, a drug known by the name Eletriptan, or of its salts. In particular, the present invention regards a process for the synthesis of Eletriptan or of its salt, comprising the following steps: a) Salifying the intermediate of Formula (6), using a dicarboxylic acid to obtain a derived salt; b) Optionally, purifying said raw salt obtained according to step a) by solvent crystallization to obtain a purified salt of the intermediate of Formula (6); c) Converting said salt of the intermediate of formula (6) according to step a) or said purified salt according to step b) into an intermediate of formula (10); d) Converting the intermediate of Formula (10) into Eletriptan or its salt.

  本发明涉及合成3-[(2R)-1-甲基吡咯烷-2-基]甲基}-5-[2-(苯磺酰基)乙基]-1H-吲哚，一种以Eletriptan命名的药物或其盐。具体而言，本发明涉及一种用于合成Eletriptan或其盐的方法，包括以下步骤：a) 用二羧酸盐化式（6）的中间体，以获得衍生盐；b) 可选地，通过溶剂结晶纯化根据步骤a)获得的原始盐，以获得式（6）的中间体的纯化盐；c) 将根据步骤a)获得的式（6）的中间体的盐或根据步骤b)获得的纯化盐转化为式（10）的中间体；d) 将式（10）的中间体转化为Eletriptan或其盐。
• PROCESS FOR PREPARATION OF ELETRIPTAN AND SALT THEREOF
  申请人：Sathe Dhananjay Govind

  公开号：US20120071669A1

  公开（公告）日：2012-03-22

  The present invention relates to an improved process for the preparation of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole or pharmaceutically acceptable salts thereof, particularly 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethyl]-1H-indole hydrobromide (Eletriptan hydrobromide). The present invention further relates to novel polymorphs of 3-(N-methyl-2(R)-pyrrolidinyl methyl)-5-[2-(phenyl sulfonyl)ethenyl]-1H-indole hydrobromide and process for preparation thereof.

  本发明涉及一种改进的制备3-(N-甲基-2(R)-吡咯烷基)-5-[2-(苯基磺酰基)乙基]-1H-吲哚或其药学上可接受的盐，特别是3-(N-甲基-2(R)-吡咯烷基)-5-[2-(苯基磺酰基)乙基]-1H-吲哚溴化氢盐（依那曲坦溴化氢盐）。本发明还涉及3-(N-甲基-2(R)-吡咯烷基)-5-[2-(苯基磺酰基)乙烯基]-1H-吲哚溴化氢盐的新晶型及其制备方法。
• 5-cyclo indole compounds
  申请人：Allelix Biopharmaceuticals, Inc.

  公开号：US05998438A1

  公开（公告）日：1999-12-07

  Described herein are compounds selective for a 5-HT.sub.1D -like receptor, which have the general formula: ##STR1## wherein A is selected from a six-membered, non-aromatic, optionally substituted carbocycle and a six-membered, non-aromatic, optionally substituted heterocycle having one or two heteroatoms selected from O, S, SO, SO.sub.2 and N.sup.4 ; R.sup.1 is selected from H and OH; n is 0 or 1 as permited by chemical structure; R.sup.2 is selected from CR.sup.5 CR.sup.6 CH.sub.2 NR.sup.7 R.sup.8 or a group of formula II, III or IV: ##STR2## R.sup.3 is selected from H and benzoyl; R.sup.4 is selected from H, loweralkyl, benzyl, loweralkylcarbonyl, loweralkylaminocarbonyl, loweralkylaminothiocarbonyl, loweralkanoyl, loweralkylaminoimide and loweralkoxy-substituted loweralkylene; R.sup.5 and R.sup.6 are independently selected from H, loweralkoxy and hydroxy; R.sup.7 and R.sup.8 are independently selected from H and loweralkyl or R.sup.7 and R.sup.8 form an alkylene bridge which, together with the nitrogen atom to which they are attached, creates an optionally substituted 3- to 6-membered ring; denotes a single or double bond; and R.sup.9, R.sup.10 and R.sup.11 are independently selected from H and loweralkyl. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of a 5-HT.sub.1D -like receptor is implicated, such as migraine.

  本文描述的是对5-HT.sub.1D-类受体具有选择性的化合物，其具有以下通式：##STR1##其中A选自一个六元非芳香族、可选择性取代的碳环和一个六元非芳香族、可选择性取代的杂环，其中含有一个或两个来自O、S、SO、SO.sub.2和N.sup.4的杂原子；R.sup.1选自H和OH；n根据化学结构允许为0或1；R.sup.2选自CR.sup.5 CR.sup.6 CH.sub.2 NR.sup.7 R.sup.8或具有以下式II、III或IV的基团：##STR2##R.sup.3选自H和苯甲酰基；R.sup.4选自H、较低烷基、苄基、较低烷基羰基、较低烷基氨基羰基、较低烷基氨基硫氨基羰基、较低烷酰基、较低烷基氨基亚胺和较低烷氧基取代的较低烷基烯；R.sup.5和R.sup.6独立选自H、较低烷氧基和羟基；R.sup.7和R.sup.8独立选自H和较低烷基，或者R.sup.7和R.sup.8形成一个与它们附着的氮原子一起构成一个可选择性取代的3-至6-成员环的烷基桥；表示单键或双键；R.sup.9、R.sup.10和R.sup.11独立选自H和较低烷基。还描述了将这些化合物用作药物来治疗刺激5-HT.sub.1D-类受体所涉及的症状，如偏头痛。
• 5-Bicycloindole compounds
  申请人：NPS Allelix Corp.

  公开号：US06329390B1

  公开（公告）日：2001-12-11

  Disclosed herein are compounds selective for a 5-HT1D receptor, the compounds having the general formula (I): Also disclosed is the use of these compounds as pharmaceuticals to treat indications where stimulation of a 5-HT1D receptor is indicated such as migrane.

  本文揭示了具有选择性5-HT1D受体的化合物，这些化合物具有通式（I）：同时，本文还揭示了将这些化合物用作药物治疗刺激5-HT1D受体的适应症，如偏头痛。
• Synthesis of 3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-5[2-(phenylsulfonyl)ethyl]-1H-indole
  申请人：Serafini Siro

  公开号：US08426612B2

  公开（公告）日：2013-04-23

  The present invention refers to the synthesis of 3-[(2R)-1-methylpyrrolidin-2-yl]methyl}-5-[2-(phenylsulfonyl)ethyl]-1H-indole, a drug known by the name Eletriptan, or of its salts. In particular, the present invention regards a process for the synthesis of Eletriptan or of its salt, comprising the following steps: a) Salifying the intermediate of Formula (6), using a dicarboxylic acid to obtain a derived salt; b) Optionally, purifying said raw salt obtained according to step a) by solvent crystallization to obtain a purified salt of the intermediate of Formula (6); c) Converting said salt of the intermediate of formula (6) according to step a) or said purified salt according to step b) into an intermediate of formula (10); d) Converting the intermediate of Formula (10) into Eletriptan or its salt.

  本发明涉及合成3-[(2R)-1-甲基吡咯烷-2-基]甲基}-5-[2-(苯磺酰基)乙基]-1H-吲哚，一种以Eletriptan命名的药物或其盐。具体而言，本发明涉及一种用以下步骤合成Eletriptan或其盐的方法：a）使用二羧酸盐化公式（6）的中间体，以获得衍生盐；b）可选地，通过溶剂结晶纯化根据步骤a）获得的原始盐，以获得公式（6）的纯化盐；c）将根据步骤a）获得的公式（6）的盐或根据步骤b）获得的纯化盐转化为公式（10）的中间体；d）将公式（10）的中间体转化为Eletriptan或其盐。